Democracy derived? New trajectories in pluripotent stem cell research.

How has the development of human induced pluripotent stem cells (hiPSCs) modified the trajectory of stem cell research? Here, coauthorship networks of stem cell research articles and analysis of cell lines used in stem cell research indicate that hiPSCs are not replacing human embryonic stem cells, but instead, the two cell types are complementary, interdependent research tools. Thus, we conclude that a ban on funding for embryonic stem cell research could have unexpected negative ramifications on the nascent field of hiPSCs.

The Responsibility to Recontact Research Participants after Reinterpretation of Genetic and Genomic Research Results.

The evidence base supporting genetic and genomic sequence-variant interpretations is continuously evolving. An inherent consequence is that a variant's clinical significance might be reinterpreted over time as new evidence emerges regarding its pathogenicity or lack thereof. This raises ethical, legal, and financial issues as to whether there is a responsibility to recontact research participants to provide updates on reinterpretations of variants after the initial analysis. There has been discussion concerning the extent of this obligation in the context of both research and clinical care. Although clinical recommendations have begun to emerge, guidance is lacking on the responsibilities of researchers to inform participants of reinterpreted results. To respond, an American Society of Human Genetics (ASHG) workgroup developed this position statement, which was approved by the ASHG Board in November 2018. The workgroup included representatives from the National Society of Genetic Counselors, the Canadian College of Medical Genetics, and the Canadian Association of Genetic Counsellors. The final statement includes twelve position statements that were endorsed or supported by the following organizations: Genetic Alliance, European Society of Human Genetics, Canadian Association of Genetic Counsellors, American Association of Anthropological Genetics, Executive Committee of the American Association of Physical Anthropologists, Canadian College of Medical Genetics, Human Genetics Society of Australasia, and National Society of Genetic Counselors.

Public Attitudes toward Consent and Data Sharing in Biobank Research: A Large Multi-site Experimental Survey in the US.

Individuals participating in biobanks and other large research projects are increasingly asked to provide broad consent for open-ended research use and widespread sharing of their biosamples and data. We assessed willingness to participate in a biobank using different consent and data sharing models, hypothesizing that willingness would be higher under more restrictive scenarios. Perceived benefits, concerns, and information needs were also assessed. In this experimental survey, individuals from 11 US healthcare systems in the Electronic Medical Records and Genomics (eMERGE) Network were randomly allocated to one of three hypothetical scenarios: tiered consent and controlled data sharing; broad consent and controlled data sharing; or broad consent and open data sharing. Of 82,328 eligible individuals, exactly 13,000 (15.8%) completed the survey. Overall, 66% (95% CI: 63%-69%) of population-weighted respondents stated they would be willing to participate in a biobank; willingness and attitudes did not differ between respondents in the three scenarios. Willingness to participate was associated with self-identified white race, higher educational attainment, lower religiosity, perceiving more research benefits, fewer concerns, and fewer information needs. Most (86%, CI: 84%-87%) participants would want to know what would happen if a researcher misused their health information; fewer (51%, CI: 47%-55%) would worry about their privacy. The concern that the use of broad consent and open data sharing could adversely affect participant recruitment is not supported by these findings. Addressing potential participants' concerns and information needs and building trust and relationships with communities may increase acceptance of broad consent and wide data sharing in biobank research.

Pancreatic cancer and melanoma related perceptions and behaviors following disclosure of CDKN2A variant status as a research result.

PURPOSE: This study examined whether participants who learned research results related to a germline CDKN2A variant known to be associated with increased risk of pancreatic cancer and malignant melanoma would pursue confirmatory testing and cancer screening, share the genetic information with health care providers and family, and change risk perceptions. METHODS: Participants were pancreas research registry enrollees whose biological sample was tested in a research laboratory for the variant. In total, 133 individuals were invited to learn a genetic research result and participate in a study about the disclosure process. Perceived cancer risk, screening intentions, and behaviors were assessed predisclosure, immediately postdisclosure, and six months postdisclosure. RESULTS: Eighty individuals agreed to participate and 63 completed the study. Immediately postdisclosure, carriers reported greater intentions to undergo pancreatic cancer and melanoma screening (p values ≤0.024). Seventy-three percent of carriers (47.5% noncarriers) intended to seek confirmatory testing within six months and 20% (2.5% noncarriers) followed through. All participants shared results with ≥1 family member. More carriers shared results with their health care provider than noncarriers (p = 0.028). CONCLUSION: Recipients of cancer genetic research results may not follow through with recommended behaviors (confirmatory testing, screening), despite stated intentions. The research result disclosure motivated follow-up behaviors among carriers more than noncarriers.

Silent Tyrosinemia Type I Without Elevated Tyrosine or Succinylacetone Associated with Liver Cirrhosis and Hepatocellular Carcinoma.

Tyrosinemia type I (TYRSN1, TYR I) is caused by fumarylacetoacetate hydrolase (FAH) deficiency and affects approximately one in 100,000 individuals worldwide. Pathogenic variants in FAH cause TYRSN1, which induces cirrhosis and can progress to hepatocellular carcinoma (HCC). TYRSN1 is characterized by the production of a pathognomonic metabolite, succinylacetone (SUAC) and is included in the Recommended Uniform Screening Panel for newborns. Treatment intervention is effective if initiated within the first month of life. Here, we describe a family with three affected children who developed HCC secondary to idiopathic hepatosplenomegaly and cirrhosis during infancy. Whole exome sequencing revealed a novel homozygous missense variant in FAH (Chr15(GRCh38):g.80162305A>G; NM_000137.2:c.424A > G; NP_000128.1:p.R142G). This novel variant involves the catalytic pocket of the enzyme, but does not result in increased SUAC or tyrosine, making the diagnosis of TYRSN1 problematic. Testing this novel variant using a rapid, in vivo somatic mouse model showed that this variant could not rescue FAH deficiency. In this case of atypical TYRSN1, we show how reliance on SUAC as a primary diagnostic test can be misleading in some patients with this disease. Augmentation of current screening for TYRSN1 with targeted sequencing of FAH is warranted in cases suggestive of the disorder.

Neurotalk: improving the communication of neuroscience research.

There is increasing pressure for neuroscientists to communicate their research and the societal implications of their findings to the public. Communicating science is challenging, and the transformation of communication by digital and interactive media increases the complexity of the challenge. To facilitate dialogue with the public in this new media landscape, we suggest three courses of action for the neuroscience community: a cultural shift that explicitly recognizes and rewards public outreach, the identification and development of neuroscience communication experts, and ongoing empirical research on the public communication of neuroscience.

'Someone should oversee it': patient perspectives on the ethical issues arising with the regulation of probiotics.

BACKGROUND: Although many probiotic products are currently available in yogurt or pill form in the United States (US), there is uncertainty surrounding the structure of regulation of these products. As more therapeutic probiotics are developed, changes to existing regulatory process in the United States may be required to meet the needs of patients and users in the population. OBJECTIVE: This study examined how patients with chronic gastrointestinal (GI) diseases view the regulation of probiotics. DESIGN: We conducted a multi-site qualitative study consisting of focus groups of patients with chronic gastrointestinal diseases at three tertiary hospitals: at [institutions removed for blinded review]. RESULTS: We conducted 22 focus groups with 136 patients with major gastrointestinal (GI) diseases between March and August 2009. Participants were not familiar with the existing regulation of probiotic products but wanted assurances of accurate labelling of strain as well as safety. Participants raised concerns that regulation of probiotics might be accompanied by greater costs, reduced access and increased involvement of pharmaceutical companies. Although participants voiced significant doubt of government regulators, they felt that products containing genetically modified probiotic strains should have oversight comparable to that of pharmaceutical drugs. DISCUSSION AND CONCLUSION: If GI patient perspectives are indicative of public perceptions of therapeutic probiotics in the United States, consumers may expect more rigorous regulation in the future while simultaneously wanting low costs, easy access and low involvement of pharmaceutical companies. Manufacturers, translational scientists, clinicians and regulators should be sensitive to consumer attitudes when designing, testing and regulating new therapeutic probiotics.

Unwarranted optimism in media portrayals of genetic research on addiction overshadows critical ethical and social concerns.

The cost of addiction in the United States, in combination with a host of new tools and techniques, has fueled an explosion of genetic research on addiction. Because the media has the capacity to reflect and influence public perception, there is a need to examine how treatments and preventive approaches projected to emerge from addiction genetic research are presented to the public. The authors conducted a textual analysis of 145 news articles reporting on genetic research on addiction from popular print media in the United States and from popular news and medical internet sites. In articles that report on prevention, the media emphasize vaccine development and identifying individuals at genetic risk through population screening. Articles that emphasize treatment often promote current pharmaceutical solutions and highlight the possibility of tailoring treatments to specific genetic variants. The authors raise concerns about the tendency of this coverage to focus on the benefits of pharmaceutical treatments and genetic-based approaches to prevention while neglecting or downplaying potential risks and ethical issues. This analysis suggests a need for more balanced, evidence-based media reporting on the potential outcomes of genetic research.

The media and behavioral genetics: Alternatives coexisting with addiction genetics.

To understand public discourse in the U.S. on genetic causation of behavioral disorders, we analyzed media representations of genetic research on addiction published between 1990 and 2010. We conclude first that the media simplistically represent biological bases of addiction and willpower as being mutually exclusive: behaviors are either genetically determined, or they are a choice. Second, most articles provide only cursory or no treatment of the environmental contribution. A media focus on genetics directs attention away from environmental factors. Rhetorically, media neglect the complexity underlying of the etiology of addiction and direct focus back toward individual causation and responsibility.

Implementing individualized medicine into the medical practice.

There is increasing recognition that genomic medicine as part of individualized medicine has a defined role in patient care. Rapid advances in technology and decreasing cost combine to bring genomic medicine closer to the clinical practice. There is also growing evidence that genomic-based medicine can advance patient outcomes, tailor therapy and decrease side effects. However the challenges to integrate genomics into the workflow involved in patient care remain vast, stalling assimilation of genomic medicine into mainstream medical practice. In this review we describe the approach taken by one institution to further individualize medicine by offering, executing and interpreting whole exome sequencing on a clinical basis through an enterprise-wide, standalone individualized medicine clinic. We present our experience designing and executing such an individualized medicine clinic, sharing lessons learned and describing early implementation outcomes.

Evaluating the process of online health information searching: a qualitative approach to exploring consumer perspectives.

BACKGROUND: The Internet is a common resource that patients and consumers use to access health-related information. Multiple practical, cultural, and socioeconomic factors influence why, when, and how people utilize this tool. Improving the delivery of health-related information necessitates a thorough understanding of users' searching-related needs, preferences, and experiences. Although a wide body of quantitative research examining search behavior exists, qualitative approaches have been under-utilized and provide unique perspectives that may prove useful in improving the delivery of health information over the Internet. OBJECTIVE: We conducted this study to gain a deeper understanding of online health-searching behavior in order to inform future developments of personalizing information searching and content delivery. METHODS: We completed three focus groups with adult residents of Olmsted County, Minnesota, which explored perceptions of online health information searching. Participants were recruited through flyers and classifieds advertisements posted throughout the community. We audio-recorded and transcribed all focus groups, and analyzed data using standard qualitative methods. RESULTS: Almost all participants reported using the Internet to gather health information. They described a common experience of searching, filtering, and comparing results in order to obtain information relevant to their intended search target. Information saturation and fatigue were cited as main reasons for terminating searching. This information was often used as a resource to enhance their interactions with health care providers. CONCLUSIONS: Many participants viewed the Internet as a valuable tool for finding health information in order to support their existing health care resources. Although the Internet is a preferred source of health information, challenges persist in streamlining the search process. Content providers should continue to develop new strategies and technologies aimed at accommodating diverse populations, vocabularies, and health information needs.

Comparative analysis of online health queries originating from personal computers and smart devices on a consumer health information portal.

BACKGROUND: The number of people using the Internet and mobile/smart devices for health information seeking is increasing rapidly. Although the user experience for online health information seeking varies with the device used, for example, smart devices (SDs) like smartphones/tablets versus personal computers (PCs) like desktops/laptops, very few studies have investigated how online health information seeking behavior (OHISB) may differ by device. OBJECTIVE: The objective of this study is to examine differences in OHISB between PCs and SDs through a comparative analysis of large-scale health search queries submitted through Web search engines from both types of devices. METHODS: Using the Web analytics tool, IBM NetInsight OnDemand, and based on the type of devices used (PCs or SDs), we obtained the most frequent health search queries between June 2011 and May 2013 that were submitted on Web search engines and directed users to the Mayo Clinic's consumer health information website. We performed analyses on "Queries with considering repetition counts (QwR)" and "Queries without considering repetition counts (QwoR)". The dataset contains (1) 2.74 million and 3.94 million QwoR, respectively for PCs and SDs, and (2) more than 100 million QwR for both PCs and SDs. We analyzed structural properties of the queries (length of the search queries, usage of query operators and special characters in health queries), types of search queries (keyword-based, wh-questions, yes/no questions), categorization of the queries based on health categories and information mentioned in the queries (gender, age-groups, temporal references), misspellings in the health queries, and the linguistic structure of the health queries. RESULTS: Query strings used for health information searching via PCs and SDs differ by almost 50%. The most searched health categories are "Symptoms" (1 in 3 search queries), "Causes", and "Treatments & Drugs". The distribution of search queries for different health categories differs with the device used for the search. Health queries tend to be longer and more specific than general search queries. Health queries from SDs are longer and have slightly fewer spelling mistakes than those from PCs. Users specify words related to women and children more often than that of men and any other age group. Most of the health queries are formulated using keywords; the second-most common are wh- and yes/no questions. Users ask more health questions using SDs than PCs. Almost all health queries have at least one noun and health queries from SDs are more descriptive than those from PCs. CONCLUSIONS: This study is a large-scale comparative analysis of health search queries to understand the effects of device type (PCs vs. SDs) used on OHISB. The study indicates that the device used for online health information search plays an important role in shaping how health information searches by consumers and patients are executed.

Stakeholder engagement: a key component of integrating genomic information into electronic health records.

Integrating genomic information into clinical care and the electronic health record can facilitate personalized medicine through genetically guided clinical decision support. Stakeholder involvement is critical to the success of these implementation efforts. Prior work on implementation of clinical information systems provides broad guidance to inform effective engagement strategies. We add to this evidence-based recommendations that are specific to issues at the intersection of genomics and the electronic health record. We describe stakeholder engagement strategies employed by the Electronic Medical Records and Genomics Network, a national consortium of US research institutions funded by the National Human Genome Research Institute to develop, disseminate, and apply approaches that combine genomic and electronic health record data. Through select examples drawn from sites of the Electronic Medical Records and Genomics Network, we illustrate a continuum of engagement strategies to inform genomic integration into commercial and homegrown electronic health records across a range of health-care settings. We frame engagement as activities to consult, involve, and partner with key stakeholder groups throughout specific phases of health information technology implementation. Our aim is to provide insights into engagement strategies to guide genomic integration based on our unique network experiences and lessons learned within the broader context of implementation research in biomedical informatics. On the basis of our collective experience, we describe key stakeholder practices, challenges, and considerations for successful genomic integration to support personalized medicine.

Improving understanding in the research informed consent process: a systematic review of 54 interventions tested in randomized control trials.

BACKGROUND: Obtaining informed consent is a cornerstone of biomedical research, yet participants comprehension of presented information is often low. The most effective interventions to improve understanding rates have not been identified. PURPOSE: To systematically analyze the random controlled trials testing interventions to research informed consent process. The primary outcome of interest was quantitative rates of participant understanding; secondary outcomes were rates of information retention, satisfaction, and accrual. Interventional categories included multimedia, enhanced consent documents, extended discussions, test/feedback quizzes, and miscellaneous methods. METHODS: The search spanned from database inception through September 2010. It was run on Ovid MEDLINE, Ovid EMBASE, Ovid CINAHL, Ovid PsycInfo and Cochrane CENTRAL, ISI Web of Science and Scopus. Five reviewers working independently and in duplicate screened full abstract text to determine eligibility. We included only RCTs. 39 out of 1523 articles fulfilled review criteria (2.6%), with a total of 54 interventions. A data extraction form was created in Distiller, an online reference management system, through an iterative process. One author collected data on study design, population, demographics, intervention, and analytical technique. RESULTS: Meta-analysis was possible on 22 interventions: multimedia, enhanced form, and extended discussion categories; all 54 interventions were assessed by review. Meta-analysis of multimedia approaches was associated with a non-significant increase in understanding scores (SMD 0.30, 95% CI, -0.23 to 0.84); enhanced consent form, with significant increase (SMD 1.73, 95% CI, 0.99 to 2.47); and extended discussion, with significant increase (SMD 0.53, 95% CI, 0.21 to 0.84). By review, 31% of multimedia interventions showed significant improvement in understanding; 41% for enhanced consent form; 50% for extended discussion; 33% for test/feedback; and 29% for miscellaneous.Multiple sources of variation existed between included studies: control processes, the presence of a human proctor, real vs. simulated protocol, and assessment formats. CONCLUSIONS: Enhanced consent forms and extended discussions were most effective in improving participant understanding. Interventions of all categories had no negative impact on participant satisfaction or study accrual. Identification of best practices for studies of informed consent interventions would aid future systematic comparisons.

Current landscape of research ethics consultation services: National survey results.

Introduction: The goal of a research ethics consultation service (RECS) is to assist relevant parties in navigating the ethical issues they encounter in conduct of research. The goal of this survey was to describe the current landscape of research ethics consultation and document if and how it has changed over the last decade. Methods: The survey instrument was based on the survey previously circulated. We included a number of survey domains from the previous survey with the goal of direct comparison of outcomes. The survey was sent to 57 RECS in the USA and Canada. Results: Forty-nine surveys were completed for an overall response rate of 86%. With the passing of 10 years, the volume of consults received by RECS surveyed has increased. The number of consults received by a subset of RECS remains low. RECS continues to receive requests for consults from a wide range of stakeholders. About a quarter of RECS surveyed actively evaluate their services, primarily through satisfaction surveys routinely shared with requestors. The number of RECS evaluating their services has increased. We identified a group of eight key competencies respondents find as key to providing RECS. Conclusions: The findings from our survey demonstrate that there have been growth and development of RECS since 2010. Further developing evaluation and competency guidelines will help existing RECS continue to grow and facilitate newly established RECS maturation. Both will allow RECS personnel to better serve their institutions and add value to the research conducted.

Political views and organizational distrust affect rural residents' willingness to share personal data for COVID-19 contact tracing: A cross-sectional survey study.

Background: We aimed to examine the attitudes of Pennsylvania rural residents toward data sharing in the setting of the COVID-19 pandemic. Specifically, we were interested in better understanding their willingness to provide personal information for contact tracing to public health staff investigating COVID-19 cases, as well as their concerns. We used a validated scale to describe the influence of distrust of healthcare organizations on their attitudes. Methods: We mailed 4000 surveys to rural residents identified from the electronic medical record of a healthcare system in central Pennsylvania. Data were entered into a REDCap database and analyzed using descriptive summaries, and both binomial and multivariable logistic regression. Results: Binomial logistic regression showed that both distrust in healthcare organizations and political values influence respondents' willingness to share information with contact tracers as well as their concerns about sharing personal data. When our multivariable model was applied, political values remained and were consistently associated with willingness to share and concerns about sharing their data. Conclusion: This study is a first step in eliciting rural residents' willingness to share personal data for contact tracing by public health officials. Understanding and addressing rural residents' willingness to share personal data and their concerns about sharing those data will help public health officials identify effective strategies for managing COVID-19 and future pandemics in rural communities. By involving community members at the ground level, public health staff can ensure residents' buy-in for the need to collect their personal data, thereby helping to mitigate the public health crises.

How patients view probiotics: findings from a multicenter study of patients with inflammatory bowel disease and irritable bowel syndrome.

BACKGROUND: Patients with inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) have access to a growing number of probiotic products marketed to improve digestive health. It is unclear how patients make decisions about probiotics and what role they expect their gastroenterologists to play as they consider using probiotics. Understanding patients' knowledge, attitudes and expectations of probiotics may help gastroenterologists engage patients in collaborative discussions about probiotics. STUDY: Focus groups were conducted with patients with IBD and IBS at the Cleveland Clinic, Mayo Clinic, and Johns Hopkins University. Inductive analytic methods were used to identify common themes and draw interpretations from focus group narratives. RESULTS: One hundred thirty-six patients participated in 22 focus groups between March and August 2009. Patients viewed probiotics as an appealing alternative to pharmaceutical drugs and understood probiotics as a more "natural," low-risk therapeutic option. Many patients were hesitant to use them without consulting their gastroenterologists. Patients would weigh the risks and benefits of probiotics, their disease severity and satisfaction with current treatments when considering probiotic use. CONCLUSIONS: Patients are interested in probiotics but have many unanswered questions about their use. Our findings suggest that patients with IBD and IBS will look to gastroenterologists and other clinicians as trustworthy advisors regarding the utility of probiotics as an alternative or supplement to pharmaceutical drugs. Gastroenterologists and other clinicians who care for patients with these diseases should be prepared to discuss the potential benefits and risks of probiotics and assist patients in making informed decisions about their use.

Experiences of patients with chronic gastrointestinal conditions: in their own words.

BACKGROUND: Irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) are chronic conditions affecting millions of individuals in the United States. The symptoms are well-documented and can be debilitating. How these chronic gastrointestinal (GI) conditions impact the daily lives of those afflicted is not well documented, especially from a patient's perspective. METHODS: Here we describe data from a series of 22 focus groups held at three different academic medical centers with individuals suffering from chronic GI conditions. All focus groups were audio recorded and transcribed. Two research team members independently analyzed transcripts from each focus group following an agreed upon coding scheme. RESULTS: One-hundred-thirty-six individuals participated in our study, all with a chronic GI related condition. They candidly discussed three broad themes that characterize their daily lives: identification of disease and personal identity, medications and therapeutics, and daily adaptations. These all tie to our participants trying to deal with symptoms on a daily basis. We find that a recurrent topic underlying these themes is the dichotomy of experiencing uncertainty and striving for control. CONCLUSIONS: Study participants' open dialogue and exchange of experiences living with a chronic GI condition provide insight into how these conditions shape day-to-day activities. Our findings provide fertile ground for discussions about how clinicians might best facilitate, acknowledge, and elicit patients' stories in routine care to better address their experience of illness.